Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by S Lim
Total Records ( 4 ) for S Lim
  S Lim , A Janzer , A Becker , A Zimmer , R Schule , R Buettner and J. Kirfel
 

Breast carcinogenesis is a multistep process involving both genetic and epigenetic changes. Since epigenetic changes like histone modifications are potentially reversible processes, much effort has been directed toward understanding this mechanism with the goal of finding novel therapies as well as more refined diagnostic and prognostic tools in breast cancer. Lysine-specific demethylase 1 (LSD1) plays a key role in the regulation of gene expression by removing the methyl groups from methylated lysine 4 of histone H3 and lysine 9 of histone H3. LSD1 is essential for mammalian development and involved in many biological processes. Considering recent evidence that LSD1 is involved in carcinogenesis, we investigated the role of LSD1 in breast cancer. Therefore, we developed an enzyme-linked immunosorbent assay to determine LSD1 protein levels in tissue specimens of breast cancer and measured very high LSD1 levels in estrogen receptor (ER)-negative tumors. Pharmacological LSD1 inhibition resulted in growth inhibition of breast cancer cells. Knockdown of LSD1 using small interfering RNA approach induced regulation of several proliferation-associated genes like p21, ERBB2 and CCNA2. Additionally, we found that LSD1 is recruited to the promoters of these genes. In summary, our data indicate that LSD1 may provide a predictive marker for aggressive biology and a novel attractive therapeutic target for treatment of ER-negative breast cancers.

  M Dobkin Bekman , M Naidich , L Rahamim , F Przedecki , T Almog , S Lim , P Melamed , P Liu , T Wohland , Z Yao , R Seger and Z. Naor
 

Most receptor tyrosine kinases and G protein-coupled receptors (GPCRs) operate via a limited number of MAPK cascades but still exert diverse functions, and therefore signal specificity remains an enigma. Also, most GPCR ligands utilize families of receptors for mediation of diverse biological actions; however, the mammalian type I GnRH receptor (GnRHR) seems to be the sole receptor mediating GnRH-induced gonadotropin synthesis and release. Signaling complexes associated with GPCRs may thus provide the means for signal specificity. Here we describe a signaling complex associated with the GnRHR, which is a unique GPCR lacking a C-terminal tail. Unlike other GPCRs, this signaling complex is preformed, and exposure of LβT2 gonadotropes to GnRH induces its dynamic rearrangement. The signaling complex includes c-Src, protein kinase C, -, and -, Ras, MAPK kinase 1/2, ERK1/2, tubulin, focal adhesion kinase (FAK), paxillin, vinculin, caveolin-1, kinase suppressor of Ras-1, and the GnRHR. Exposure to GnRH (5 min) causes MAPK kinase 1/2, ERK1/2, tubulin, vinculin, and the GnRHR to detach from c-Src, but they reassociate within 30 min. On the other hand, FAK, paxillin, the protein kinase Cs, and caveolin-1 stay bound to c-Src, whereas kinase suppressor of Ras-1 appears in the complex only 30 min after GnRH stimulation. GnRH was found to activate ERK1/2 in the complex in a c-Src-dependent manner, and the activated ERK1/2 subsequently phosphorylates FAK and paxillin. In parallel, caveolin-1, FAK, vinculin, and paxillin are phosphorylated on Tyr residues apparently by GnRH-activated c-Src. Receptor tyrosine kinases and GPCRs translocate ERK1/2 to the nucleus to phosphorylate and activate transcription factors. We therefore propose that the role of the multiprotein signaling complex is to sequester a cytosolic pool of activated ERK1/2 to phosphorylate FAK and paxillin at focal adhesions.

  Y. J Park , J. W Yoon , K. I Kim , Y. J Lee , K. W Kim , S. H Choi , S Lim , D. J Choi , K. H Park , J. H Choh , H. C Jang , S. Y Kim , B. Y Cho and C. Lim
  Background

Some studies have proposed that subclinical hypothyroidism (SCH) has adverse effects on the cardiovascular system, but little is known about the effect on patients undergoing cardiovascular operations. We examined the influence of preoperative SCH on postoperative outcome in patients undergoing coronary artery bypass grafting (CABG).

Methods

Among patients who underwent CABG between July 2005 and June 2007 at Seoul National University Bundang Hospital, 224 with normal thyroid function and 36 with SCH were enrolled. Preoperative risks and postoperative outcomes were evaluated prospectively without thyroid hormone replacement.

Results

There were no significant differences in primary outcomes (major adverse cardiovascular events) and secondary outcomes such as wound problems, mediastinitis, leg infection, respiratory complications, delirium, or reoperation during the same hospitalization. However, patients with SCH had a higher incidence of postoperative atrial fibrillation than those with normal thyroid function after adjustment for age, gender, body mass index, and other independent variables such as emergency operation, the use of cardiopulmonary bypass, combined valvular operation, preoperative creatinine levels, left ventricular systolic dysfunction, and nonuse of β-blockers (45.5% vs 29%; odds ratio, 2.552; 95% confidence interval, 1.117 to 5.830; p = 0.026).

Conclusions

SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation. However, it is still unproven whether preoperative thyroxine replacement therapy for patients with SCH might prevent postoperative atrial fibrillation after CABG.

  Y Li , S Lim , D Hoffman , P Aspenstrom , H. J Federoff and D. A. Rempe
 

Mitochondrial transport is critical for maintenance of normal neuronal function. Here, we identify a novel mitochondria protein, hypoxia up-regulated mitochondrial movement regulator (HUMMR), which is expressed in neurons and is markedly induced by hypoxia-inducible factor 1 (HIF-1). Interestingly, HUMMR interacts with Miro-1 and Miro-2, mitochondrial proteins that are critical for mediating mitochondrial transport. Interestingly, knockdown of HUMMR or HIF-1 function in neurons exposed to hypoxia markedly reduces mitochondrial content in axons. Because mitochondrial transport and distribution are inextricably linked, the impact of reduced HUMMR function on the direction of mitochondrial transport was also explored. Loss of HUMMR function in hypoxia diminished the percentage of motile mitochondria moving in the anterograde direction and enhanced the percentage moving in the retrograde direction. Thus, HUMMR, a novel mitochondrial protein induced by HIF-1 and hypoxia, biases mitochondria transport in the anterograde direction. These findings have broad implications for maintenance of neuronal viability and function during physiological and pathological states.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility